FDA Approves MAGE-A4 IHC 1F9 pharmDx as Diagnostic Tool in Patients With Synovial Sarcoma

Updated at 11:10 am on August 2, 2024.

The FDA has approved melanoma-associated antigen A4 (MAGE-A4) immunohistochemistry (IHC) 1F9 pharmDx (SK032; Agilent Technologies) as a diagnostic tool to aid in identifying patients who have synovial sarcoma and may be eligible for treatment with the newly approved MAGE-A4-directed engineered T-cell receptor (TCR) T-cell therapy afamitresgene autoleucel (afami-cel, Tecelra; Adaptimmune). The diagnostic tool is the first in vitro diagnostic for MAGE-A4 that is available on the market.¹

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MAGE-A4 is a cancer testis antigen that is overexpressed in various cancers, such as synovial sarcoma. MAGE-A4 IHC 1F9 pharmDx is an IHC assay that is used to detect the expression of MAGE-A4 in formalin-fixed paraffin-embedded (FFPE) synovial sarcoma tissue. Additionally, MAGE-A4 positivity is a biomarker of eligibility for treatment with afami-cel in hose with synovial sarcoma.¹

Further, afami-cel was also approved by the FDA for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive with the A*02:01P, A*02:02P, A*02:03P, or A*02:06P HLA antigens, and whose tumor expresses the MAGE-A4 antigen determined by the authorized companion devices, such as MAGE-A4 IHC 1F9 pharmDx. The treatment is a prescription medicine and the first FDA-approved engineered TCR T-cell therapy for a solid tumor cancer.^1,2

In a study published in Molecular Therapy Methods and Clinical Development that assessed the eligibility rate for TCR T-cell therapies based on different biomarker screening methods, MAGE-A4 IHC demonstrated efficacy, and its precision was validated. In the study, an anti-MAGE-A4 antibody (clone OTI1F9) showed specific staining of MAGE-A4 without cross-reactivity to MAGE-A1, -A2, -A3, -A6, -A9 (in MAGE-A-transduced NAML6 cell lines), -A10 (in the Mel526 cell line with endogenous high MAGE-A10 expression), and -A11 and -A12 (in Mel624). The anti-MAGE-A4 antibody demonstrated a rate staining (0.28%) to MAGE-A8-transduced MALN6 cell line—which is a high MAGE-A8 expression in approximately 56% of cells—as well as minor cross-reactivity to MAGE-A10-transduced NALM6 cell line, artificial systems that have extremely high MAGE-A8 or MAGE-A10 expression.³

According to the analytical validation, the tumor and tissue samples included showed different MAGE-A4 prevalence in a broad range of solid tumors, but not in normal tissues with the exception of testis and placenta. Additionally, the precision of the MAGE-A4 IHC clinical trial assay was validated at the cutoff (≥30% at ≥2+ intensity) with an 80% and higher inter-run and intra-run concordance, which was mostly 90% and higher. In addition, inter-lab assay transfer demonstrated 100% concordance on a series of samples of multiple indications. Further, pathologists’ scoring demonstrated 80% or higher (mostly ≥90%) intra-reader and inter-reader concordance for a series of samples of multiple indications. The results also demonstrated that accuracy evaluations indicated high reliability when assessing eligibility for clinical trials investigation afami-cel and uzatresgene autoleucel (uza-cel; Adaptimmune).³

“MAGE-A4 plays a significant role in cancer research and holds promise as a therapeutic target. The FDA’s approval of Agilent’s MAGE-A4 IHC 1F9 pharmDx will expand treatment options for individuals diagnosed with synovial sarcoma,” said Lou Welebob, vice president and general manager of Agilent’s Pathology Division, in a news release. “This endorsement amplifies Agilent’s pioneering role in shaping companion diagnostics for groundbreaking cancer therapies.”¹

References

1. Businesswire. Agilent Receives FDA Approval for MAGE-A4 IHC 1F9 pharmDx as a Diagnostic Tool for Use with Newly Approved TCR T-Cell Therapy. News release. August 2, 2024. Accessed August 2, 2024. https://www.businesswire.com/news/home/20240802261119/en/Agilent-Receives-FDA-Approval-for-MAGE-A4-IHC-1F9-pharmDx-as-a-Diagnostic-Tool-for-Use-with-Newly-Approved-TCR-T-Cell-Therapy

2. US Food & Drug Administration. FDA Approves First Gene Therapy to Treat Adults with Metastatic Synovial Sarcoma. News release. August 2, 2024. Accessed August 2, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-metastatic-synovial-sarcoma

3. Wang T, Navenot JM, Rafail S, et al. Identifying MAGE-A4-positive tumors for TCR T cell therapies in HLA-A∗02-eligible patients. Mol Ther Methods Clin Dev. 2024;32(2):101265. Published 2024 May 14. doi:10.1016/j.omtm.2024.101265